NCT03483103已完成2 期
A Phase 2 Study of Lisocabtagene Maraleucel (JCAR017) as Second-Line Therapy in Adult Patients With Aggressive B-cell NHL (017006)
Juno Therapeutics, a Subsidiary of Celgene112 个研究点 分布在 1 个国家目标入组 74 人开始时间: 2018年7月27日最近更新:
适应症
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 74
- 试验地点
- 112
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
This is a Phase 2, open-label, multicenter study to determine the efficacy and safety of lisocabtagene maraleucel (JCAR017) in adult subjects who have relapsed from, or are refractory to, a single line of immunochemotherapy for aggressive B-cell non-Hodgkin lymphoma (NHL) and are ineligible for hematopoietic stem cell transplant (based on age, performance status, and/or comorbidities). Subjects will receive treatment with lisocabtagene maraleucel and will be followed for 2 years for safety, pharmacokinetics and biomarkers, disease status, quality of life, and survival.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmation of relapsed or refractory aggressive B-cell non-Hodgkin lymphoma of the following histology at relapse: diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS; de novo or transformed follicular lymphoma [tFL]), high-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (double/triple hit lymphoma [DHL/THL]), and follicular lymphoma Grade 3B per WHO 2016 classification
- •Previous treatment must include treatment with a single line of chemoimmunotherapy containing an anthracycline and a CD20-targeted agent
- •Subjects must be deemed ineligible for both high-dose chemotherapy and hematopoietic stem cell transplant (based on age, performance status and/or comorbidities) while also having adequate organ function for CAR T cell treatment.
- •Positron emission tomography (PET)-positive disease
- •Histological confirmation of diagnosis at last relapse. Enough tumor material must be available for central confirmation of diagnosis, otherwise a new tumor biopsy is mandated.
- •ECOG performance status of 0, or 1, or 2
- •Adequate vascular access for leukapheresis procedure (either peripheral line or surgically-placed line)
- •Subjects must agree to use appropriate contraception
- •Subjects must agree to not donate blood, organs, semen, and egg cells for usage in other individuals for at least 1 year following lymphodepleting chemotherapy
排除标准
- •Subjects with central nervous system (CNS)-only involvement by malignancy (note: subjects with secondary CNS involvement are allowed on study)
- •History of another primary malignancy that has not been in remission for at least 2 years.
- •Previous treatment with CD19-targeted therapy, with the exception of prior lisocabtagene maraleucel treatment in this protocol for subjects receiving retreatment
- •Active hepatitis B or hepatitis C infection at the time of screening
- •History of or active human immunodeficiency virus (HIV) infection at the time of screening
- •Uncontrolled systemic fungal, bacterial, viral or other infection despite appropriate antibiotics or other treatment at the time of leukapheresis or lisocabtagene maraleucel administration
- •History of any one of the following cardiovascular conditions within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association, cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant cardiac disease
- •History or presence of clinically relevant CNS pathology
- •Pregnant or nursing women
- •Subject does not meet protocol-specified washout periods for prior treatments
- •Prior hematopoietic stem cell transplant
- •Progressive vascular tumor invasion, thrombosis, or embolism
- •Venous thrombosis or embolism not managed on stable regimen of anticoagulation
- •Uncontrolled medical, psychological, familial, sociological, or geographical conditions
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: From first dose to disease progression, end of study, the start of another anticancer therapy, or hematopoietic stem cell transplantation (up to approximately 24 months)
Overall response rate is the percent of participants with a best overall response (BOR) of either complete response (CR) or partial reasons (PR) based on the Independent Review Committee (IRC) assessment recorded from the time of JCAR017 treatment until disease progression, end of study, the start of another anticancer therapy or JCAR017 retreatment. CR = Score 1, 2, or 3 with or without a residual mass on the positron emission tomography 5-point scale (PET 5PS). A score of 3 in many patients indicates a good prognosis with standard treatment. PR = Score 4 or 5b with reduced uptake compared with baseline and residual mass(es) of any size. PET 5PS = 1- no uptake above background; 2- uptake ≤ mediastinum; 3- uptake \> mediastinum but ≤ liver; 4- uptake moderately \> liver; 5- uptake markedly higher than liver and/or new lesions; X- new areas of uptake unlikely to be related to lymphoma.
次要结局
- Change From Baseline of Hematology Laboratory Results: Hemoglobin(Baseline and Day 29)
- Number of Participants With Any Treatment-Emergent Adverse Events (TEAEs)(From first dose to 90 days following first dose (up to approximately 90 days))
- Overall Survival (OS)(From first dose to date of death (up to approximately 24 months))
- Progression-Free Survival (PFS)(From first dose to progressive disease (PD) or death (up to approximately 24 months))
- PK Parameters of JCAR017 in Blood as Assessed by qPCR: Tmax(From first dose to up to 24 months)
- Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Fatigue Subscale(Baseline and Day 29)
- Change From Baseline of Chemistry Laboratory Results: Albumin(Baseline and Day 29)
- Change From Baseline of Hematology Laboratory Results: Leukocytes, Lymphocytes, Neutrophils, Platelets(Baseline and Day 29)
- Duration of Response (DOR)(From first dose to up to approximately 24 months)
- Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Pain Subscale(Baseline and Day 29)
- Change From Baseline of Chemistry Laboratory Results: Alanine Aminotransferase, Aspartate Aminotransferase, Lactate Dehydrogenase(Baseline and Day 29)
- Change From Baseline of Chemistry Laboratory Results: Bilirubin, Creatinine, Direct Bilirubin, Urate(Baseline and Day 29)
- Change From Baseline of Chemistry Laboratory Results: Calcium Corrected, Magnesium, Phosphate, Potassium, Sodium(Baseline and Day 29)
- PK Parameters of JCAR017 in Blood as Assessed by qPCR: Cmax(From first dose to up to 24 months)
- PK Parameters of JCAR017 in Blood as Assessed by qPCR: AUC (0-28)(From first dose to up to 24 months)
- Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Physical Functioning Subscale(Baseline and Day 29)
- Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Cognitive Functioning Subscale(Baseline and Day 29)
- Complete Response (CR) Rate(From first dose to disease progression, end of study, the start of another anticancer therapy, or hematopoietic stem cell transplant (up to approximately 24 months))
- Duration of Response (DOR) in Participants With Complete Response (CR)(From first dose to up to approximately 24 months)
- Event-Free Survival (EFS)(From first dose to death from any cause, progressive disease (PD), or starting a new anticancer therapy (up to approximately 24 months))
- Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Insomnia Subscale(Baseline and Day 29)
- Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Global Health/QoL Subscale(Baseline and Day 29)
- Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Diarrhea Subscale(Baseline and Day 29)
- Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Dyspnea Subscale(Baseline and Day 29)
- The Number of Participants That Were Hospitalized For Adverse Events, Prophylaxis, Other(From first dose after JCAR017 infusion to up to approximately 24 months)
- Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Role Functioning Subscale(Baseline and Day 29)
- Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Constipation Subscale(Baseline and Day 29)
- Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Financial Difficulties Subscale(Baseline and Day 29)
- Health-Related Quality of Life (HRQoL) Assessed by the EuroQol Instrument EQ-5D-5L(Baseline and Day 29)
- Numbers of Intensive Care Unit (ICU) Inpatient Days(From first dose after JCAR017 infusion to up to approximately 24 months)
- Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Emotional Functioning Subscale(Baseline and Day 29)
- Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Social Functioning Subscale(Baseline and Day 29)
- Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Appetite Loss Subscale(Baseline and Day 29)
- Mean Score in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-30) Nausea/Vomiting Subscale(Baseline and Day 29)
- Health-Related Quality of Life (HRQoL) Assessed by the FACT-Lym Subscale(Baseline and Day 29)
- Numbers of Non-intensive Care Unit (ICU) Inpatient Days(From first dose after JCAR017 infusion to up to approximately 24 months)
研究者
研究点 (112)
Loading locations...
相似试验
已完成
2 期
A Safety Trial of Lisocabtagene Maraleucel (JCAR017) for Relapsed and Refractory (R/R) B-cell Non-Hodgkin Lymphoma (NHL) in the Outpatient Setting (TRANSCEND-OUTREACH-007)Lymphoma, Non-HodgkinLymphoma, B-CellLymphomaLymphoma, Large B-Cell, DiffuseNeoplasmsNeoplasms by Histologic TypeLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DisorderNCT03744676Juno Therapeutics, a Subsidiary of Celgene104
已完成
2 期
Study of Axicabtagene Ciloleucel Given With Steroids In Participants With Relapsed Or Refractory Large B-Cell LymphomaRelapsed or Refractory Large B-cell LymphomaNCT05459571Kite, A Gilead Company35
进行中（未招募）
2 期
A Study to Evaluate ICP-022 in Patients With R/R PCNSL and SCNSLSecondary Central Nervous System LymphomaPCNSLNCT04438044Beijing InnoCare Pharma Tech Co., Ltd.61
招募中
2 期
Study of BEBT-109 in Subjects With Non-Small Cell Lung Cancer Carrying EGFR Exon 20 Insertion MutationsNon Small Cell Lung CancerNCT06514027BeBetter Med Inc30
招募中
1 期
Phase 1/2 Clinical Study of HY07121 Powder for Solution for Infusion in Patients With Advanced Solid TumorsSafetyTolerabilityEfficacyNCT06639256Sichuan Huiyu Pharmaceutical Co., Ltd258